Trichodion, a new inhibitor of inflammatory signal transduction pathways from a Trichosporiella species

FEBS Letters

Erkel, Gerhard¹ 

[1] Institut für Biotechnologie und Wirkstoff-Forschung e.V., Erwin-Schrödinger-Str. 56, D-67663 Kaiserslautern, Germany

关键词: JAK/STAT pathway;    Inhibitor;    Inflammatory signal transduction pathway;    COX;    cyclooxygenase;    NOS;    NO-synthase;    IFN;    interferon;    LPS;    lipopolysaccharide;    TPA;    12-O-tetradecanoylphorbol-13-acetate;   

DOI  :  10.1016/S0014-5793(00)01784-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

In a search for new inhibitors of the IFN-γ mediated signal transduction in HeLa S3 cells using secreted alkaline phosphatase (SEAP) as reporter gene, the novel pyran-dione trichodion was isolated from fermentations of the imperfect fungus Trichosporiella sp. 20-95. The compound inhibits the IFN-γ mediated expression of the reporter gene with IC₅₀ values of 21–42 μM (5–10 μg/ml). The NF-κB and AP-1 mediated expression of the reporter gene are inhibited with IC₅₀ values of 42–84 μM (10–20 μg/ml) and 21 μM (5 μg/ml) respectively. Western blotting with COX-2 and NOS II antibodies showed that the expression of both proinflammatory enzymes is almost completely inhibited at 21–42 μM (5–10 μg/ml) in LPS/IFN-γ stimulated J774 mouse macrophages. Studies on the mode of action of the compound revealed that the inhibition of the NF-κB dependent pathway is due to the stabilization of the IκB protein and the inhibition of the IFN-γ dependent signaling is caused by an inhibition of the phosphorylation of the STAT1α transcription factor.

【 授权许可】

Unknown